{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:38Z","timestamp":1787014178087,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T00:00:00Z","timestamp":1389571200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000311","name":"Tuberous Sclerosis Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000311","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004815","name":"The Isaac Newton Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004815","id-type":"DOI","asserted-by":"crossref"}]},{"name":"UK National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Kings College London"},{"name":"The South London and Maudsley NHS Foundation Trust"},{"name":"NIHR Senior Investigators Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Infantile spasms (\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      ) have long been suspected to be a risk factor for impairment in intellectual development, but there are no controlled, prospective longitudinal data in well\u2010characterized conditions to confirm this suspicion. We tested the hypothesis in a longitudinal study of children with tuberous sclerosis (\n                      <jats:styled-content style=\"fixed-case\">TS<\/jats:styled-content>\n                      ), who have a high risk of developing\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eleven infants with\n                      <jats:styled-content style=\"fixed-case\">TS<\/jats:styled-content>\n                      were recruited and studied longitudinally using the\n                      <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>\n                      ullen\n                      <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                      cales of\n                      <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>\n                      arly\n                      <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\n                      earning. Seizure histories were assessed using a structured parent interview and by review of medical notes. Intellectual development was examined in relation to the onset and length of exposure to\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      and other types of seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six children developed\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      and five children developed other types of seizure disorders. Among those that developed\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      , estimated mean\n                      <jats:styled-content style=\"fixed-case\">IQ<\/jats:styled-content>\n                      dropped significantly (nonparametric test for trend p\u00a0=\u00a00.002) from 92 (prior to onset of spasms) to 73 (after exposure to\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      for a month or less) and 62 (after exposure to\n                      <jats:styled-content style=\"fixed-case\">IS<\/jats:styled-content>\n                      for more than a month). By contrast, there was no significant drop in estimated\n                      <jats:styled-content style=\"fixed-case\">IQ<\/jats:styled-content>\n                      among the five infants exposed to other types of seizure disorders (nonparametric test for trend p\u00a0=\u00a00.9). All six children exposed to infantile spasms developed clinically significant intellectual impairment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These data provide the first clear evidence of clinically significant, dose dependent, impairment in intellectual development following exposure to infantile spasms. The mechanisms underlying this developmental impairment and methods for preventing it require in depth study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.12484","type":"journal-article","created":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T18:01:49Z","timestamp":1389636109000},"page":"108-116","source":"Crossref","is-referenced-by-count":47,"title":["Intellectual development before and after the onset of infantile spasms: A controlled prospective longitudinal study in tuberous sclerosis"],"prefix":"10.1111","volume":"55","author":[{"given":"Ayla","family":"Humphrey","sequence":"first","affiliation":[{"name":"Section of Developmental Psychiatry University of Cambridge Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"MacLean","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Cambridge Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George B.","family":"Ploubidis","sequence":"additional","affiliation":[{"name":"Department of Population Studies Faculty of Epidemiology and Population Health London School of Hygiene and Tropical Medicine University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Granader","sequence":"additional","affiliation":[{"name":"Children's National Medical Center Washington District of Columbia U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Clifford","sequence":"additional","affiliation":[{"name":"Social Genetic &amp; Developmental Psychiatry Centre &amp; Department of Child &amp; Adolescent Psychiatry Institute of Psychiatry King's College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maisy","family":"Haslop","sequence":"additional","affiliation":[{"name":"Department of Clinical Psychology Royal Holloway University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G.R.","family":"Neville","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.W.","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Cambridge Cambridge United Kingdom"},{"name":"East Anglian Medical Genetics Service Addenbrooke's Hospital Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick F.","family":"Bolton","sequence":"additional","affiliation":[{"name":"Social Genetic &amp; Developmental Psychiatry Centre &amp; Department of Child &amp; Adolescent Psychiatry Institute of Psychiatry King's College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Tuberous Sclerosis 2000 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1992.tb02306.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.00353.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(01)00300-X"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejpn.2001.0538"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2012.05.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/316951"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2009.160606"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1788"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21317"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(01)00299-6"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2004.12.003"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-004-0383-1"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2006.tb01324.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.01.007"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000280579.04974.c0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2011.03.010"},{"key":"e_1_2_10_19_1","volume-title":"Mullen scales of early learning","author":"Mullen E","year":"1995"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2003.026815"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.03127.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05117.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291707000177"},{"key":"e_1_2_10_24_1","first-page":"149","article-title":"MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment","volume":"16","author":"Shepherd CW","year":"1995","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_10_25_1","volume-title":"Stata statistical software. 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